{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360004229809857536.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1002/2211-5463.12374"}},{"identifier":{"@type":"URI","@value":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2F2211-5463.12374"}},{"identifier":{"@type":"URI","@value":"http://api.wiley.com/onlinelibrary/chorus/v1/articles/10.1002%2F2211-5463.12374"}},{"identifier":{"@type":"URI","@value":"https://febs.onlinelibrary.wiley.com/doi/pdf/10.1002/2211-5463.12374"}},{"identifier":{"@type":"PMID","@value":"29511612"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Regucalcin confers resistance to amyloid‐β toxicity in neuronally differentiated <scp>PC</scp>12 cells"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Amyloid‐β (Aβ), a primary component of amyloid plaques, has been widely associated with the pathogenesis of Alzheimer's disease. The Ca<jats:sup>2+</jats:sup>‐binding protein regucalcin (RGN) plays multiple roles in maintaining cell functions by regulating intracellular calcium homeostasis, various signaling pathways, and gene expression systems. Here, we investigated the functional role of RGN against Aβ‐induced cytotoxicity in neuronally differentiated <jats:styled-content style=\"fixed-case\">PC</jats:styled-content>12 cells. Overexpression of RGN reduced Aβ‐induced apoptosis by reducing mitochondrial dysfunction and caspase activation. It also attenuated Aβ‐induced reactive oxygen species production and oxidative damage and decreased Aβ‐induced nitric oxide (NO) overproduction, upregulation of inducible NO synthase by nuclear factor‐κB, and nitrosative damage. Interestingly, the genetic disruption of RGN increased the susceptibility of neuronally differentiated <jats:styled-content style=\"fixed-case\">PC</jats:styled-content>12 cells to Aβ toxicity. Thus, RGN possesses antioxidant activity against Aβ‐induced oxidative and nitrosative stress and may play protective roles against Aβ‐induced neurotoxicity in Alzheimer's disease.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1420845751143762304","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"80285189"},{"@type":"NRID","@value":"1000080285189"},{"@type":"NRID","@value":"9000382231313"},{"@type":"NRID","@value":"9000018768529"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/mura_tomi_meijo33919"}],"foaf:name":[{"@value":"Tomiyasu Murata"}],"jpcoar:affiliationName":[{"@value":"Laboratory of Analytical Neurobiology Faculty of Pharmacy Meijo University Nagoya Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004229809858058","@type":"Researcher","foaf:name":[{"@value":"Masayoshi Yamaguchi"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology and Laboratory Medicine David Geffen School of Medicine University of California, Los Angeles (UCLA) CA USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1420282801185382016","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"30625463"},{"@type":"NRID","@value":"1000030625463"},{"@type":"NRID","@value":"9000351097599"},{"@type":"NRID","@value":"9000319547045"},{"@type":"NRID","@value":"9000239615498"},{"@type":"NRID","@value":"9000344803391"},{"@type":"NRID","@value":"9000291275209"},{"@type":"NRID","@value":"9000018768528"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/sk_"}],"foaf:name":[{"@value":"Susumu Kohno"}],"jpcoar:affiliationName":[{"@value":"Division of Oncology and Molecular Biology Cancer Research Institute Kanazawa University Ishikawa Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1420845751162650112","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"50283619"},{"@type":"NRID","@value":"1000050283619"},{"@type":"NRID","@value":"9000351097612"},{"@type":"NRID","@value":"9000319562933"},{"@type":"NRID","@value":"9000242446753"},{"@type":"NRID","@value":"9000239615510"},{"@type":"NRID","@value":"9000017330934"},{"@type":"NRID","@value":"9000238964731"},{"@type":"NRID","@value":"9000022296872"},{"@type":"NRID","@value":"9000002044530"},{"@type":"NRID","@value":"9000319547048"},{"@type":"NRID","@value":"9000409867769"},{"@type":"NRID","@value":"9000409578926"},{"@type":"NRID","@value":"9000409575797"},{"@type":"NRID","@value":"9000005709592"},{"@type":"NRID","@value":"9000024108422"},{"@type":"NRID","@value":"9000239615502"},{"@type":"NRID","@value":"9000291275210"},{"@type":"NRID","@value":"9000018462743"},{"@type":"NRID","@value":"9000344803398"},{"@type":"NRID","@value":"9000409015899"},{"@type":"NRID","@value":"9000406034684"},{"@type":"NRID","@value":"9000409575795"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/chiakitakahashi"}],"foaf:name":[{"@value":"Chiaki Takahashi"}],"jpcoar:affiliationName":[{"@value":"Division of Oncology and Molecular Biology Cancer Research Institute Kanazawa University Ishikawa Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004229809857666","@type":"Researcher","foaf:name":[{"@value":"Mitsumi Kakimoto"}],"jpcoar:affiliationName":[{"@value":"Laboratory of Analytical Neurobiology Faculty of Pharmacy Meijo University Nagoya Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004229809858062","@type":"Researcher","foaf:name":[{"@value":"Yukiko Sugimura"}],"jpcoar:affiliationName":[{"@value":"Laboratory of Analytical Neurobiology Faculty of Pharmacy Meijo University Nagoya Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004229809857927","@type":"Researcher","foaf:name":[{"@value":"Mako Kamihara"}],"jpcoar:affiliationName":[{"@value":"Laboratory of Analytical Neurobiology Faculty of Pharmacy Meijo University Nagoya Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004229809858051","@type":"Researcher","foaf:name":[{"@value":"Kiyomi Hikita"}],"jpcoar:affiliationName":[{"@value":"Laboratory of Analytical Neurobiology Faculty of Pharmacy Meijo University Nagoya Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004229809857931","@type":"Researcher","foaf:name":[{"@value":"Norio Kaneda"}],"jpcoar:affiliationName":[{"@value":"Laboratory of Analytical Neurobiology Faculty of Pharmacy Meijo University Nagoya Japan"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"22115463"},{"@type":"EISSN","@value":"22115463"}],"prism:publicationName":[{"@value":"FEBS Open Bio"}],"dc:publisher":[{"@value":"Wiley"}],"prism:publicationDate":"2018-01-20","prism:volume":"8","prism:number":"3","prism:startingPage":"349","prism:endingPage":"360"},"reviewed":"false","dc:rights":["http://creativecommons.org/licenses/by/4.0/"],"url":[{"@id":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2F2211-5463.12374"},{"@id":"http://api.wiley.com/onlinelibrary/chorus/v1/articles/10.1002%2F2211-5463.12374"},{"@id":"https://febs.onlinelibrary.wiley.com/doi/pdf/10.1002/2211-5463.12374"}],"createdAt":"2018-01-03","modifiedAt":"2024-12-26","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Research%20Articles","dc:title":"Research Articles"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040000781913857152","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"16K08252"},{"@type":"JGN","@value":"JP16K08252"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16K08252/"}],"notation":[{"@language":"ja","@value":"多様な細胞機能を制御するレギュカルチンの病態生理的役割の解明"},{"@language":"en","@value":"Elucidation of pathophysiological role of regucalcin regulating diverse cell functions"}]},{"@id":"https://cir.nii.ac.jp/crid/1040000781956908160","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"17H03576"},{"@type":"JGN","@value":"JP17H03576"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17H03576/"}],"notation":[{"@language":"ja","@value":"RBがん抑制遺伝子の代謝制御機構"},{"@language":"en","@value":"Metabolic regulation by RB tumor suppressor gene"}]},{"@id":"https://cir.nii.ac.jp/crid/1040000781972371200","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"17K14992"},{"@type":"JGN","@value":"JP17K14992"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17K14992/"}],"notation":[{"@language":"ja","@value":"PGAMによるエピジェネティクスリモデリングを介したがん悪性化機構の解明"},{"@language":"en","@value":"Tumor progression through epigenetics remodeling by RB-PGAM"}]},{"@id":"https://cir.nii.ac.jp/crid/1040000781975311488","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"17K19586"},{"@type":"JGN","@value":"JP17K19586"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17K19586/"}],"notation":[{"@language":"ja","@value":"パッセンジャー変異合成致死性による新規がん代謝治療標的探索"},{"@language":"en","@value":"Drug discovery based on collateral lethality"}]},{"@id":"https://cir.nii.ac.jp/crid/1040282256935597824","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"17H05615"},{"@type":"JGN","@value":"JP17H05615"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PUBLICLY-17H05615/"}],"notation":[{"@language":"ja","@value":"乳腺上皮・乳がんにおけるRB モザイシズムと細胞競合"},{"@language":"en","@value":"RB mosaicism and cell competition in mammary epithelial and cancer cells"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360011143583968384","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Senescence Marker Protein 30 (SMP30) Expression in Eukaryotic Cells: Existence of Multiple Species and Membrane Localization"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011144602437248","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Alzheimer's Disease: Genes, Proteins, and 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lipopolysaccharide‐induced inflammatory responses in pancreatic MIN6 β‐cells and RAW264.7 macrophages"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285714667275392","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Increased regucalcin gene expression extends survival in breast cancer patients: Overexpression of regucalcin suppresses the proliferation and metastatic bone activity in MDA-MB-231 human breast cancer cells in vitro"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285714667316096","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Prolonged survival in hepatocarcinoma patients with increased regucalcin gene expression: HepG2 cell proliferation is suppressed by overexpression of regucalcin in vitro"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292618952056064","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Senescence Marker Protein-30 Protects Mice Lungs from Oxidative Stress, Aging, and Smoking"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292619443628288","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The diverse roles of calcium-binding protein regucalcin in cell biology: from tissue expression and signalling to disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292619562957696","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Induction of cytochrome c-mediated apoptosis by amyloid β 25-35 requires functional mitochondria"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292621443717120","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The transcriptional regulation of regucalcin gene expression"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292621602734848","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Amyloid-β–induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks"}]},{"@id":"https://cir.nii.ac.jp/crid/1360572092574016256","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Regucalcin enhances adipocyte differentiation and attenuates inflammation in 3T3‐L1 cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848664620658304","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Prolonged survival in pancreatic cancer patients with increased regucalcin gene expression: Overexpression of regucalcin suppresses the proliferation in human pancreatic cancer MIA PaCa-2 cells in vitro"}]},{"@id":"https://cir.nii.ac.jp/crid/1360853567793825280","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Cytotoxic activity of dimeric acridone alkaloids derived from <i>Citrus</i> plants towards human leukaemia HL-60 cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855570106532352","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Genomic cloning and chromosomal assignment of rat regucalcin gene"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855570727645056","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Role of regucalcin in calcium signaling"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137044930550528","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137046099237760","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Alternatively spliced variants of the regucalcin gene in various human normal and tumor tissues"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418518742415360","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Amyloid-β Peptide Fibrils Induce Nitro-Oxidative Stress in Neuronal Cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418518969346048","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"How mitochondria produce reactive oxygen species"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418519202415616","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Regucalcin increases Ca<sup>2+</sup>‐ATPase activity in the mitochondria of brain tissues of normal and transgenic rats"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418520129837440","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Amyloid β-induced Changes in Nitric Oxide Production and Mitochondrial Activity Lead to Apoptosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418520952142080","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The anti-apoptotic effect of regucalcin is mediated through multisignaling pathways"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418520983091072","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The Role of Regucalcin in Nuclear Regulation of Regenerating Liver"}]},{"@id":"https://cir.nii.ac.jp/crid/1361699995508796928","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"SMP30 deficiency causes increased oxidative stress in 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tsAM5D"}]},{"@id":"https://cir.nii.ac.jp/crid/1362262943656207872","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Purification of senescence marker protein-30 (SMP30) and tis androgen-independent decrease with age in the rat liver"}]},{"@id":"https://cir.nii.ac.jp/crid/1362262944707154304","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Regucalcin and cell regulation: role as a suppressor protein in signal transduction"}]},{"@id":"https://cir.nii.ac.jp/crid/1362262944847266176","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Crystal Structure of Human Senescence Marker Protein 30: Insights Linking Structural, Enzymatic, and Physiological Functions,"}]},{"@id":"https://cir.nii.ac.jp/crid/1362262945850390144","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Ergothioneine rescues PC12 cells from β-amyloid-induced apoptotic death"}]},{"@id":"https://cir.nii.ac.jp/crid/1362544419015596416","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Hippocampal Neurons Predisposed to Neurofibrillary Tangle Formation Are Enriched in Type II Calcium/Calmodulin-Dependent Protein Kinase"}]},{"@id":"https://cir.nii.ac.jp/crid/1362544419254851328","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"SMP30 deficiency in mice causes an accumulation of neutral lipids and phospholipids in the liver and shortens the life span"}]},{"@id":"https://cir.nii.ac.jp/crid/1362544420319231744","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Pathways towards and away from Alzheimer's disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1362544421157975168","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825894662127744","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Nitric Oxide and Nitroxidative Stress in Alzheimer's Disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825895802510848","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Neuroprotective and neurorescuing effects of isoform‐specific nitric oxide synthase inhibitors, nitric oxide scavenger, and antioxidant against beta‐amyloid toxicity"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107368673326464","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Involvement of the Nitric Oxide Pathway in Synaptic Dysfunction Following Amyloid Elevation in Alzheimer's Disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107369381572864","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Critical analysis of Alzheimer rsquo s amyloid-beta nbsp toxicity to mitochondria"}]},{"@id":"https://cir.nii.ac.jp/crid/1363107371370898048","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Redox modulation by S-nitrosylation contributes to protein misfolding, mitochondrial dynamics, and neuronal synaptic damage in neurodegenerative diseases"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388843303244288","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Calcium Signaling and Amyloid Toxicity in Alzheimer Disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388843611604608","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Calpain Mediates Calcium-Induced Activation of the Erk1,2 MAPK Pathway and Cytoskeletal Phosphorylation in Neurons"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388844512985088","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Cytotoxicity of Intracellular Aβ\n                    <sub>42</sub>\n                    Amyloid Oligomers Involves Ca\n                    <sup>2+</sup>\n                    Release from the Endoplasmic Reticulum by Stimulated Production of Inositol Trisphosphate"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388844842212864","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Involvement of regucalcin as a suppressor protein in human carcinogenesis: insight into the gene therapy"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388845005053696","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Phosphorylation of tau at serine 416 by Ca<sup>2+</sup>/calmodulin‐dependent protein kinase II in neuronal soma in brain"}]},{"@id":"https://cir.nii.ac.jp/crid/1363670318926622336","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Role of regucalcin in cell nuclear regulation: involvement as a transcription 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